Numerous neuroanatomical and neurophysiological studies have been performed which suggest a hierarchial pattern of organization of autonomic centers in the CNS which subtends virtually every level of the nervous system. In this scheme, caudal centers such as the medullary nucleus tracus solitarius (NTS) are "hard wired" to primary autonomic afferent and efferent connections; intermediate centers such as the pontine parabrachial nucleus (PBN) play a key role in the relay and integration of autonomic data to and from more caudal and rostral centers, and rostral centers such as the hypothalamic paraventricular nucleus (PVN) integrate autonomic responses with more complex neuroendocrine and behavioral responses. Intrinsic to the organizational pattern are important neuropeptide systems which affect the transmission of signals resulting in autonomic homeostasis. Among them, POMC derivatives, vasopressin and CRF are emerging as potent peptides in autonomic control. We propose studies which address the intrinsic neuropeptidergic organization and patterns of interconnectivity in brainstem. Our continued studies to analyze by retrograde/immunocytochemical methods will focus on three specific regions which possess "dual" innervation by both arcuate and NTS POMC neurons. A detailed study of the topography, morphometry and trajectory of CRF in brainstem, with major emphasis upon demonstration of all fiber projection will delineate innervation of autonomic areas by CRF. The immunocytochemical analysis for the identification of receptor images and post-synaptic second order neurons will employ the use of well characterized anti-idiotype antibodies. These studies which will be subjected to image analysis will add new dimensions to receptor identification. Finally, in recognition to the fact that the ultimate objective of our research is to better understand the functions of the brain with application to the human, several investigations are proposed. These immunocytochemical studies will provide much needed information regarding the topographic localization and pattern of co-localization of VP, POMC and CRF as well as putative vasopressin receptors, following which single section double staining methods will be utilized to suggest patterns of interaction, in the human, of these neuropeptide systems.